The Strength have played in competitive finals only thrice in history, the last of which came in 1968. They have a chance to end that drought after being drawn in a relatively easy group which also features India and Cambodia.
However, their form has been poor lately, losing each of their last four games, scoring just once.
Afghanistan have not played in any major tournaments before and enter the match on the back of a 2-0 friendly loss to Vietnam last Wednesday.
Hong Kong vs Afghanistan Head-To-Head
Hong Kong and Afghanistan have clashed just once in history - in the 1984 Asia Cup, which ended in a goalless draw.
Hong Kong Form Guide (all competitions): L-L-L-L
Afghanistan Form Guide (all competitions): L-L-L-W-W
Hong Kong vs Afghanistan Team News
Head coach Jorn Andersen has called up 25 players for this month's qualifying campaign, all of whom are locally based players.
All-time record appearance-maker Yapp Hung Fai, who has 79 caps with the side, could extend his record further by taking his position between the sticks once again.
The Lions of Khorasan have called up a 35-man squad for their qualifying fixtures against Hong Kong, India and Cambodia.
Midfielder Faysal Shayesteh is just one goal away from claiming the title as Afghanistan's all-time top-scorer. He would also become the first player in history to hit double figures in terms of goals scored.
Hong Kong vs Afghanistan Predicted XI
Hong Kong (4-3-3): Yapp Hung Fai; Yue Tze Nam, Yu Wai Lim, Fung Hing Wa, Wong Tsz Ho; Chan Siu Kwan, Huang Yang, Wong Wai; Law Tsz Chun, Matt Orr, Jahangir Khan.
Afghanistan (4-2-3-1): Ovays Azizi; David Najem, Noor Husin, Sharif Mukhammad, Milad Intezar; Abassin Alikhil, Noor Husin; Omran Haydary, Omid Popalzay, Omid Musawi; Noralla Amiri.
Hong Kong vs Afghanistan Prediction
Afghanistan are the better side on paper and can give Hong Kong a tough run for their money.
The Strength have lost in their last few games and have recently struggled to offer attacking threats.
The Lions of Khorasan should win this one.
Prediction: Hong Kong 1-2 Afghanistan